Die vorliegende Studie analysierte Osteoprotegerin-Serumwerte in einer großen Patientenkohorte mit akutem ST-Hebungs-Myokardinfarkt und konnte erstmals eine mögliche Verbindung mit Parametern einer myokardialen Schädigung in der kardialen Magnetresonanztomographie aufzeigen, zudem konnte anhand erhöhter Osteoprotegerin-Messwerte (≥75. Perzentile) 24 Stunden nach akutem ST-Hebungs-Myokardinfarkt unabhängig auf das vermehrte Auftreten von MACE geschlossen werden.:1 Abkürzungsverzeichnis 2 Abbildungsverzeichnis 3 Tabellenverzeichnis 4 Einleitung 4.1 Einführung 4.2 ST-Streckenhebungs-Myokardinfarkt 4.2.1 Einführung 4.2.2 Pathophysiologie des Myokardinfarktes und verschiedene Typen 4.2.2.1 Myokardinfarkt Typ 1 4.2.2.2 Myokardinfarkt Typ 2 4.2.2.3 Myokardinfarkt Typ 3 4.2.2.4 Myokardinfarkt Typ 4 4.2.2.5 Myokardinfarkt Typ 5 4.2.2.6 Weitere Definitionen des Myokardinfarktes oder der Myokardschädigung 4.2.3 Klinisches Bild des ST-Streckenhebungs-Myokardinfarktes 4.2.4 Diagnostik des ST-Streckenhebungs-Myokardinfarktes 4.2.5 Therapie des ST-Streckenhebungs-Myokardinfarktes 4.2.5.1 Behandlungspfad beim ST-Streckenhebungs-Myokardinfarkt 4.2.5.2 Perkutane Koronarintervention 4.2.5.3 Medikamentöse Therapie beim ST-Streckenhebungs- Myokardinfarkt 4.2.6 Killip- und TIMI-Klassifikation 4.3 Osteoprotegerin 4.3.1 Einführung 4.3.2 Struktur und Synthese von Osteoprotegerin 4.3.3 Osteoprotegerin und Osteoporose 4.3.4 Osteoprotegerin und Atherosklerose 4.3.4.1 Einführung 4.3.4.2 Der „Duke Jeopardy Score“ 4.3.4.3 Osteoprotegerin beim akuten Koronarsyndrom 4.3.4.4 Osteoprotegerin und Infarktgröße 4.4 Kardiale Magnetresonanztomographie 4.4.1 Einführung 4.4.2 Myokardiale Magnetresonanztomographie und Parameter des akuten Myokardschadens 5 Zielstellung der Arbeit 6 Material und Methoden 6.1 Einführung 6.2 Studienort, -zeitraum und Ethik 6.3 Einschlusskriterien 6.4 Primäre perkutane Koronarintervention und nachfolgende Behandlung 6.5 Bestimmung der Osteoprotegerin-Serumspiegel 6.6 Kardiale Magnetresonanztomographie und Analyse des Reperfusionsschadens 6.7 Langzeitnachbeobachtung und klinische Endpunkte 6.8 Statistische Analyse 7 Ergebnisse 7.1 Studiencharakteristika 7.2 Studienablauf 7.3 Patientencharakteristika 7.4 Verlauf der Osteoprotegerin-Serumwerte 7.5 Osteoprotegerin und schwerwiegende kardiovaskuläre Ereignisse 7.6 Osteoprotegerin und kardiale Magnetresonanztomographie 7.7 Osteoprotegerin und das angiographische „no-reflow“-Phänomen 7.8 Osteoprotegerin und „no-reflow“-Phänomen in der kardialen Magnetresonanztomographie 8 Diskussion 8.1 Einführung 8.2 Diskussion der Ergebnisse 8.2.1 Osteoprotegerin und Myokardschaden 8.2.2 Osteoprotegerin und Pathophysiologie des akuten ST- Streckenhebungs-Myokardinfarktes 8.2.3 Osteoprotegerin und Prognose 8.3 Limitationen 8.4 Zusammenfassung und Ausblick 9 Zusammenfassung der Arbeit 10 Literaturverzeichnis 11 Anhang 11.1 Übersicht über die verwendeten Geräte 11.2 Übersicht über die verwendeten Reagenzien 11.3 Erklärung über die eigenständige Abfassung der Arbeit 11.4 Lebenslauf 11.5 Publikation 11.6 Danksagung

Background: ST-elevation acute myocardial infarction (STEMI) represents one of the leading causes of death. The time of STEMI onset has a circadian rhythm with a peak during diurnal hours, and the occurrence of STEMI follows a seasonal pattern with a salient peak of cases in the winter months and a marked reduction of cases in the summer months. Scholars investigated the reason behind the winter peak, suggesting that environmental and climatic factors concur in STEMI pathogenesis, but no studies have investigated whether the circadian rhythm is modified with the seasonal pattern, in particular during the summer reduction in STEMI occurrence. Methods and Results: Here, we provide a multiethnic and multination epidemiological study (from both hemispheres at different latitudes, n=2270 cases) that investigates whether the circadian variation of STEMI onset is altered in the summer season. The main finding is that the difference between numbers of diurnal (6:00 to 18:00) and nocturnal (18:00 to 6:00) STEMI is markedly decreased in the summer season, and this is a prodrome of a complex mechanism according to which the circadian rhythm of STEMI time onset seems season dependent. Conclusions: The “summer shift” of STEMI to the nocturnal interval is consistent across different populations, and the sunshine duration (a measure related to cloudiness and solar irradiance) underpins this season-dependent circadian perturbation. Vitamin D, which in our results seems correlated with this summer shift, is also primarily regulated by the sunshine duration, and future studies should investigate their joint role in the mechanisms of STEMI etiogenesis.

Background: ST-elevation acute myocardial infarction (STEMI) represents one of the leading causes of death. The time of STEMI onset has a circadian rhythm with a peak during diurnal hours, and the occurrence of STEMI follows a seasonal pattern with a salient peak of cases in the winter months and a marked reduction of cases in the summer months. Scholars investigated the reason behind the winter peak, suggesting that environmental and climatic factors concur in STEMI pathogenesis, but no studies have investigated whether the circadian rhythm is modified with the seasonal pattern, in particular during the summer reduction in STEMI occurrence. Methods and Results: Here, we provide a multiethnic and multination epidemiological study (from both hemispheres at different latitudes, n=2270 cases) that investigates whether the circadian variation of STEMI onset is altered in the summer season. The main finding is that the difference between numbers of diurnal (6:00 to 18:00) and nocturnal (18:00 to 6:00) STEMI is markedly decreased in the summer season, and this is a prodrome of a complex mechanism according to which the circadian rhythm of STEMI time onset seems season dependent. Conclusions: The “summer shift” of STEMI to the nocturnal interval is consistent across different populations, and the sunshine duration (a measure related to cloudiness and solar irradiance) underpins this season-dependent circadian perturbation. Vitamin D, which in our results seems correlated with this summer shift, is also primarily regulated by the sunshine duration, and future studies should investigate their joint role in the mechanisms of STEMI etiogenesis.